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This study aimed to develop a simulation model that accounts for skin-specific properties in order to predict photothermal damage during skin laser treatment. To construct a computational model, surface geometry information was obtained from an optical coherence tomography image, and the absorption coefficient of the skin was determined through spectrophotometry. The distribution of the internal light dose inside the skin medium was calculated using the light propagation model based on the Monte Carlo method. The photothermal response due to the absorption of laser light was modeled by a finite difference time domain model to solve the bio-heat transfer equation. The predicted depth and area of the damaged lesions from the simulation model were compared to those measured in ex vivo porcine skin. The present simulation model gave acceptable predictions with differences of approximately ∼10% in both depth and area.

Biodegradable metals have received limited attention for application in transdermal drug delivery, although metallic microneedles (MNs) and iontophoresis have been thoroughly researched for this purpose. Here, we present Mg as a salient candidate for an MN electrode. Its metallic properties enable the application of voltage to enhance the diffusion of charged drug molecules, while hydrogen gas generated during Mg corrosion prevents its application to electrodes. The Mg MN electrode was fabricated using a nanosecond laser, and the amount of hydrogen gas were measured with applied potential during iontophoresis. Accordingly, an appropriate potential window for iontophoresis was established based on the combined effect of enhanced drug diffusion by applied electric potential and impediment from hydrogen generation. The dye permeation tests of the Mg MN on the porcine skin demonstrated the combined effect of the Mg MN and iontophoresis. The dye migration decreased at higher voltages due to excess hydrogen generation and the corrosion of needle tips, both making the diffusion of charged dye molecules along the Mg MN surface harder. These results demonstrate optimal potential range of Mg MN electrodes for transdermal drug delivery with an electric field and bubble generation during iontophoresis. Graphical Abstract

Developing a universal culture platform that manipulates cell fate is one of the most important tasks in the investigation of the role of the cellular microenvironment. This study focuses on the application of topographical and electrical field stimuli to human myogenic precursor cell (hMPC) cultures to assess the influences of the adherent direction, proliferation, and differentiation, and induce preconditioning-induced therapeutic benefits. First, a topographical surface of commercially available culture dishes was achieved by femtosecond laser texturing. The detachable biphasic electrical current system was then applied to the hMPCs cultured on laser-textured culture dishes. Laser-textured topographies were remarkably effective in inducing the assembly of hMPC myotubes by enhancing the orientation of adherent hMPCs compared with flat surfaces. Furthermore, electrical field stimulation through laser-textured topographies was found to promote the expression of myogenic regulatory factors compared with nonstimulated cells. As such, we successfully demonstrated that the combined stimulation of topographical and electrical cues could effectively enhance the myogenic maturation of hMPCs in a surface spatial and electrical field-dependent manner, thus providing the basis for therapeutic strategies., Graphical abstract Image 1, Highlights • We applied simultaneous topographical and electrical stimuli on human myogenic precursor cells. • Combined topographical/electrical stimulation enhanced the maturation of hMPCs. • hMPCs that simultaneously experienced stimulations contributed to muscle regeneration and angiogenesis in vivo. • Laser modification for commercially available plastic culture products provides the basis for future therapeutic strategies.

Synthetic biomaterials are used to overcome the limited quantity of human-derived biomaterials and to impart additional biofunctionality. Although numerous synthetic processes have been developed using various phases and methods, currently commonly used processes have some issues, such as a long process time and difficulties with extensive size control and high-concentration metal ion substitution to achieve additional functionality. Herein, we introduce a rapid synthesis method using a laser-induced hydrothermal process. Based on the thermal interaction between the laser pulses and titanium, which was used as a thermal reservoir, hydroxyapatite particles ranging from nanometer to micrometer scale could be synthesized in seconds. Further, this method enabled selective metal ion substitution into the apatite matrix with a controllable concentration. We calculated the maximum temperature achieved by laser irradiation at the surface of the thermal reservoir based on the validation of three simplification assumptions. Subsequent linear regression analysis showed that laser-induced hydrothermal synthesis follows an Arrhenius chemical reaction. Hydroxyapatite and Mg

Despite innovative advances in stent technology, restenosis remains a crucial issue for the clinical implantation of stents. Reactive oxygen species (ROS) are known to potentially accelerate re-endothelialization and lower the risk of restenosis by selectively controlling endothelial cells and smooth muscle cells. Recently, several studies have been conducted to develop biodegradable polymeric stents. As biodegradable polymers are not electrically conductive, double metallic layers are required to constitute a galvanic couple for ROS generation. Here, we report a new biodegradable hybrid material composed of a biodegradable polymer substrate and double anodic/cathodic metallic layers for enhancing re-endothelialization and suppressing restenosis. Pure Zn and Mg films (3 μm thick) were deposited onto poly

The utilization of cell-manipulating techniques reveals information about biological behaviors suited to address a wide range of questions in the field of life sciences. Here, we introduced an on/off switchable physical stimuli technique that offers precise stimuli for reversible cell patterning to allow regulation of the future direction of adherent cellular behavior by leveraging enzymatically degradable alginate hydrogels with defined chemistry and topography. As a proof of concept, targeted muscle cells adherent to TCP exhibited a reshaped structure when the hydrogel-based physical stimuli were applied. This simple tool offers easy manipulation of adherent cells to reshape their morphology and to influence future direction depending on the characteristics of the hydrogel without limitations of time and space. The findings from this study are broadly applicable to investigations into the relationships between cells and physiological extracellular matrix environments as well as has potential to open new horizons for regenerative medicine with manipulated cells.

In the semiconductor manufacturing process, the inner walls of the equipment are coated with yttrium-based oxides for etch resistance against plasma exposure. Yttrium oxyfluoride (YOF) particle synthesis and coating methods have been actively studied owing to their high erosion resistance compared to Y2O3 and Al2O3. Owing to the formation of a rough and porous coating layer by thermal spray-coating, the coating layer disintegrates, as the etching process has been conducted for a long time. Laser-induced synthesis and coating technology offer several advantages, including simplified process steps, ease of handling, and formation of a dense coating layer on the target material. In this study, YOF was coated on an aluminum substrate using a modified precursor solution. The NaF and HMTA were added to the precursor solution, resulting in enhanced synthetic reactivity and stabilizing the oxides. The material coated on the surface was analyzed based on the characteristics of composition, chemical bonding, and phase identification. We found that the coating properties can be improved by using an appropriate combination of modified precursor solutions and laser parameters. Therefore, the findings in this study are expected to be utilized in the field of coating technology.

Fibrin gels have been extensively used for three-dimensional cell culture, bleeding control, and molecular and cell therapies because the fibrous networks facilitate biomolecular and cell transport. However, a small window for gelation makes it difficult to handle the gels for desired preparation and transport. Several methods developed to control gelation rates often alter the microstructure, thereby affecting the mechanical response. We hypothesized that a particle designed to discharge thrombin cargos in response to an external stimulus, such as H2O2, would provide control of the gelation rate over a broad range while strengthening the gel. We examined this hypothesis by assembling poly (lactic-co-glycolic acid) (PLGA) particles loaded with thrombin and MnO2 nanosheets that decompose H2O2 to O2 gas. The resulting particles named as catalytic microgelator were mixed with fibrinogen solution or blood containing 0.2mM H2O2. Due to the increased internal pressure, these particles released a 3-fold larger mass of thrombin than PLGA particles loaded only with thrombin. As a consequence, catalytic microgelators increased the gelation time by one order of magnitude and the elastic modulus by a factor of two compared with the fibrin gel formed by directly mixing fibrinogen and thrombin in solution. These catalytic microgelators also served to clot blood, unlike PLGA particles loaded with thrombin. The resulting blood clot was also more rigid than the blood clot formed by thrombin solution. The results of this study would serve as a new paradigm in controlling gelation kinetics of pre-gel solution and mechanical properties of the post-gel matrix.

Lasers that exhibit monochromaticity, directionality, coherence, and focusability have been used in health care and defense industries for over five decades. Recently, the application of lasers in medical and biomedical devices has increased significantly. Considering biomedical devices and materials are attached to the skin or implanted into the body, the immune response, inflammation control, cell adhesion, migration, and biocompatibility of the device must be investigated. Therefore, researchers are actively studying laser processing technology to control these problems. In this study, we present the different types of selective laser–material interaction techniques used in biomedical devices and materials and their characteristics. Additionally, we demonstrate how to determine the type and related processes associated with biomedical devices based on the desired treatment by depicting examples, principles, and process conditions applied to the device.

Background Exposure to air particulate matter (PM) is associated with various diseases in the human respiratory system. To date, most in vitro studies showing cellular responses to PM have been performed in cell culture using a single cell type. There are few studies considering how multicellular networks communicate in a tissue microenvironment when responding to the presence of PM. Here, an in vitro three-dimensional (3D) respiratory mucosa-on-a-chip, composed of human nasal epithelial cells, fibroblasts, and endothelial cells, is used to recapitulate and better understand the effects of urban particulate matter (UPM) on human respiratory mucosa. Results We hypothesized that the first cells to contact with UPM, the nasal epithelial cells, would respond similar to the tissue microenvironment, and the 3D respiratory mucosa model would be a suitable platform to capture these events. First, whole transcriptome analysis revealed that UPM induced gene expression alterations in inflammatory and adhesion-related genes in human nasal epithelial cells. Next, we developed an in vitro 3D respiratory mucosa model composed of human nasal epithelial cells, fibroblasts, and endothelial cells and demonstrated that the model is structurally and functionally compatible with the respiratory mucosa. Finally, we used our model to expose human nasal epithelial cells to UPM, which led to a disruption in the integrity of the respiratory mucosa by decreasing the expression of zonula occludens-1 in both the epithelium and endothelium, while also reducing vascular endothelial cadherin expression in the endothelium. Conclusions We demonstrate the potential of the 3D respiratory mucosa model as a valuable tool for the simultaneous evaluation of multicellular responses caused by external stimuli in the human respiratory mucosa. We believe that the evaluation strategy proposed in the study will move us toward a better understanding of the detailed molecular mechanisms associated with pathological changes in the human respiratory system.

In this study, we developed aptamer-conjugated hydroxyapatite (Apt-HA) that promotes bone regeneration and angiogenesis. The 3R02 bivalent aptamer specific to vascular endothelial growth factor (VEGF) was grafted to the hydroxyapatite (HA) surface. Apt-HA was tested for its VEGF protein capture ability to determine the optimal aptamer concentration immobilized on the HA. Apt-HA showed higher VEGF protein capture ability, and faster growth of human umbilical vein endothelial cell (HUVEC) compared to a neat HA with no cytotoxic effects on human osteoblasts. To examine in vivo angiogenesis and bone regeneration, Apt-HA and HA were bilaterally implanted into rabbit tibial metaphyseal defects and analyzed after eight weeks using micro-CT, histology, and histomorphometry. Apt-HA showed significantly increased the volume of new bones, the percentage of bone, and the density of bone mineral in cortical bone. Apt-HA also exhibited the enhanced bone formation at the cortical region in a histomorphometric analysis. Finally, Apt-HA showed significantly increased blood vessel number compared to a neat HA. In summary, the engineered Apt-HA has potential as a bone graft material that may simultaneously promote bone regeneration and angiogenesis. STATEMENT OF SIGNIFICANCE: This work presents a functional hydroxyapatite bone graft using a DNA-based aptamer which overcomes the limitations of existing bone graft materials, which use bound signaling peptides. DNA aptamer immobilized hydroxyapatite enhances the in vitro proliferation of human umbilical vascular endothelial cells as well as in vivo angiogenesis and bone regeneration. DNA aptamer immobilized hydroxyapatite shows no cytotoxic effect on human osteoblasts.

Melanoma is one of the skin cancers caused by various causes. Since the patients often do not feel pain that melanoma is mistaken for benign skin diseases. However, melanoma has the risk of multiplying rapidly and spreading easily through metastasis. It is important to treat it through chemo- or radiotherapy after surgical resection. Immunotherapy is a relatively new cancer treatment, which has shown longer survival rates than conventional cancer treatments in some cases. Cytokines or immune checkpoint blockers are the common immunotherapy strategies for melanoma. However, there are still melanoma patients who have not been benefited by immunotherapies. To overcome the limitations of current immunotherapy approaches, studies are underway to find new immunomodulators and various combinational immunotherapies. In this review, the existing treatments for melanoma are introduced and efforts to find optimal immunotherapy conditions for melanoma treatment have been summarized. Attempts to study the immunotherapy of melanoma with biochip technologies that simulate the body's microenvironment have also been summarized.

Despite significant advances in the design of metallic materials for bare metal stents (BMSs), restenosis induced by the accumulation of smooth muscle cells (SMCs) has been a major constraint on improving the clinical efficacy of stent implantation. Here, a new strategy for avoiding this issue by utilizing hydrogen peroxide (H2O2) generated by the galvanic coupling of nitinol (NiTi) stents and biodegradable magnesium-zinc (Mg-Zn) alloys is reported. The amount of H2O2 released is carefully optimized via the biodegradability engineering of the alloys and by controlling the immersion time to selectively inhibit the proliferation and function of SMCs without harming vascular endothelial cells. Based on demonstrations of its unique capabilities, a fully metallic stent with antirestenotic functionality was successfully fabricated by depositing Mg layers onto commercialized NiTi stents. The introduction of surface engineering to yield a patterned Mg coating ensured the maintenance of a stable interface between Mg and NiTi during the process of NiTi stent expansion, showing high feasibility for clinical application. This new concept of an inert metal/degradable metal hybrid system based on galvanic metal coupling, biodegradability engineering, and surface patterning can serve as a novel way to construct functional and stable BMSs for preventing restenosis.

β-Glucan, a polysaccharide biopolymer, is one of the constituents of cell walls of microorganisms, basidiomycetes, and plants. It has pathogen-associated molecular patterns, recognizing specific im...

The excessive initial corrosion rate of Mg is a critical limitation in the clinical application of biodegradable Mg implants because the device loses its fixation strength before the fractured bone heals. This study suggests a new approach to overcome this hurdle by accelerating tissue regeneration instead of delaying the implant biodegradation. As angiogenesis is an essential process in early bone regeneration, a Mg implant coated with electrospun nanofibers containing nitric oxide (NO), which physiologically promotes angiogenesis, is designed. The integrated device enables adjustable amounts of NO to be stored on the NO donor-conjugated nanofiber coating, stably delivered, and released to the fractured bone tissue near the implanted sites. An in vitro corrosion test reveals no adverse effect of the released NO on the corrosion behavior of the Mg implant. Simultaneously, the optimal concentration level of NO released from the implant significantly enhances tube network formation of human umbilical vein endothelial cells without any cytotoxicity problem. This indicates that angiogenesis can be accelerated by combining NO-releasing nanofibers with a Mg implant. With its proven feasibility, the proposed approach could be a novel solution for the initial stability problem of biodegradable Mg implants, leading to successful bone fixation.

Mesenchymal stromal cells (MSCs) secreting multiple growth factors and immunomodulatory cytokines are promising for regenerative medicine. To further enhance their secretory activity, efforts have emerged to tether nanosized carriers of secretory stimuli, named nanostimulators, to the MSC surface by forming nonchemical bonds. Despite some successes, there is a great need to improve the retention of nanostimulators during transport through a syringe needle, where high shear stress exerted on the cell surface separates them. To this end, we hypothesize that poly(lactic-co-glycolic acid)-block-hyaluronic acid (PLGA-HA) conjugated with integrin-binding RGD peptides, denoted PLGA-HA-RGD, can form nanostimulators that remain on the cell surface stably during the injection. The resulting HA-CD44 and RGD-integrin bonds would synergistically increase the adhesion strength of nanostimulators. Interestingly, nanostimulators prepared with PLGA-HA-RGD show 3- to 6-fold higher retention than those made with PLGA-HA. Therefore, the PLGA-HA-RGD nanostimulators induced MSCs to secrete 1.5-fold higher vascular endothelial growth factors and a 1.2-fold higher tissue inhibitor of matrix metalloproteinase-1 as compared to PLGA-HA nanostimulators. Consequently, MSCs tethered with PLGA-HA-RGD nanostimulators served to stimulate endothelial cell activities to form a blood vessel-like endothelial lumen with increased length and number of junctions. The nanostimulator design strategy would also be broadly applicable to regulate, protect, and home a broad array of therapeutic or immune cells by tethering carriers with bioactive molecules of interest.

Mg has received much attention as a next-generation implantable material owing to its biocompatibility, bone-like mechanical properties, and biodegradability in physiological environments. The application of various polymer coatings has been conducted in the past to reduce the rapid formation of hydrogen gas and the local change in pH during the initial phase of the chemical reaction with the body fluids. Here, we propose femtosecond (fs) laser-mediated Mg surface patterning for significant enhancement of the binding strength of the coating material, which eventually reduces the corrosion rate. Analyses of the structural, physical, crystallographic, and chemical properties of the Mg surface have been conducted in order to understand the mechanism by which the surface adhesion increases between Mg and the polymer coating layer. Depending on the fs laser conditions, the surface structure becomes rough owing to the presence of several microscaled pits and grooves of nanoporous MgO, resulting in a tightly bonded poly(lactic-co-glycolic acid) (PLGA) layer. The corrosion rate of the PLGA-coated, fs laser-treated Mg is considerably slow compared with the non-treated Mg; the treated Mg is also more biocompatible compared with the non-treated Mg. The fs laser-based surface modification technique offers a simple and quick method for introducing a rough coating on Mg; further, it does not require any chemical treatment, thereby overcoming a potential obstacle for its clinical use.

While a clear operating field during endoscopy is essential for accurate diagnosis and effective surgery, fogging or biofouling of the lens can cause loss of visibility during these procedures. Conventional cleaning methods such as the use of an irrigation unit, anti-fogging surfactant, or particle-based porous coatings infused with lubricants have been used but proven insufficient to prevent loss of visibility. Herein, a mechanically robust anti-fogging and anti-biofouling endoscope lens was developed by forming a lubricant-infused directly engraved nano-/micro-structured surface (LIDENS) on the lens. This structure was directly engraved onto the lens via line-by-line ablation with a femtosecond laser. This directly engraved nano/microstructure provides LIDENS lenses with superior mechanical robustness compared to lenses with conventional particle-based coatings, enabling the maintenance of clear visibility throughout typical procedures. The LIDENS lens was chemically modified with a fluorinated self-assembled monolayer (F-SAM) followed by infusion of medical-grade perfluorocarbon lubricants. This provides the lens with high transparency (> 70%) along with superior and long-lasting repellency towards various liquids. This excellent liquid repellency was also shown to be maintained during blood dipping, spraying, and droplet condensation experiments. We believe that endoscopic lenses with the LIDENS offer excellent benefits to endoscopic surgery by securing clear visibility for stable operation.

The topical delivery of siRNA-based therapies has opened new avenues for the treatment of skin disorders. The use of siRNA as a therapeutic, however, is limited due to its rapid degradation and poor cellular uptake. Furthermore, the top layer of skin, the stratum corneum, is a major barrier to the delivery of topical agents. There is an unmet need for efficient topical formulations for delivering siRNA to the site of action. In this study, we used 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or lipofectamine to prepare a nanocarrier for delivering siRNA against glyceraldehyde 3-phosphate dehydrogenase (GAPDH); GAPDH expression was then evaluated at the cellular level. In addition, a dermal transport assay was designed and implemented to evaluate the penetration and delivery efficacy of siRNA in pig skin using lipid nanocarriers. The delivery of siRNA with the use of a lipid nanocarrier was significantly better than the delivery of siRNA without it. Thus, Our findings identify lipid nanocarriers as excellent candidates for the transdermal delivery of siRNA for gene silencing in the skin and thus for applications in related preclinical models.

Utilization of biodegradable metals in biomedical fields is emerging because it avoids high-risk and uneconomic secondary surgeries for removing implantable devices. Mg and its alloys are considered optimum materials for biodegradable implantable devices because of their high biocompatibility; however, their excessive and uncontrollable biodegradation is a difficult challenge to overcome. Here, we present a novel method of inhibiting Mg biodegradation by utilizing reduced nicotinamide adenine dinucleotide (NADH), an endogenous cofactor present in all living cells. Incorporating NADH significantly increases Mg corrosion resistance by promoting the formation of thick and dense protective layers. The unique mechanism by which NADH enables corrosion inhibition was discovered by combined microscopic and spectroscopic analyses. NADH is initially self-adsorbed onto the surface of Mg oxide layers, preventing Cl− ions from dissolving Mg oxides, and later recruits Ca2+ ions to form stable Ca-P protective layers. Furthermore, stability of NADH as a corrosion inhibitor of Mg under physiological conditions were confirmed using cell tests. Moreover, excellent cell adhesion and viability to Mg treated with NADH shows the feasibility of introduction of NADH to Mg-based implantable system. Our strategy using NADH suggests an interesting new way of delaying the degradation of Mg and demonstrates potential roles for biomolecules in the engineering the biodegradability of metals.

Posterior capsular opacification (PCO) is the most common complication of cataract surgery. PCO is due to the proliferation, migration, and epithelial-to-mesenchymal transition of the residual lens epithelial cells (LECs) within the lens capsule. As surface topography influences cellular response, we investigated the effect of modulating the dimensions of periodic nano-textured patterns on the surface of an intraocular lens material to regulate lens epithelial cell functions such as cell adhesion, migration, orientation, and proliferation. Patterned poly(HEMA) samples were prepared by a femtosecond laser microfabrication, and the behaviors of human B-3 LECs were observed on groove/ridge patterns with widths varying from 5 to 40 µm. In the presence of ridge and groove patterns, the adherent cells elongated along the direction of the patterns, and f-actin of the cells was spread to a lesser extent on the nano-textured groove surfaces. Both single and collective cell migrations were significantly inhibited in the perpendicular direction of the patterns on the nano-textured micro-patterned samples. We also fabricated the patterns on the curved surface of a commercially available intraocular lens for in vivo evaluation. In vivo results showed that a patterned IOL could help suppress the progression of PCO by inhibiting cell migration from the edge to the center of the IOL. Our reports demonstrate that nano- and microscale topographical patterns on a biomaterial surface can regulate cellular behavior when it is implanted into animals.

A new antibacterial strategy for Ti has been developed without the use of any external antibacterial agents and surface treatments. By combining Mg alloys with Ti, H2O2, which is an oxidizing agent that kills bacteria, was spontaneously generated near the surface of Ti. Importantly, the H2O2 formation kinetics can be precisely controlled by tailoring the degradation rates of Mg alloys connected to Ti. Through microstructural and electrochemical modification of Mg with alloying elements (Ca, Zn), the degradation rates of Mg alloys were controlled, and the H2O2 release kinetics was accelerated when the degradation rate of Mg alloys increased. With the introduction of an in vivo assessment platform comprised of Escherichia coli (E. coli) and transgenic zebrafish embryos, we are able to design optimized antibacterial systems (Ti-Mg and Ti-Mg-3wt% Zn) that can selectively eradicate E. coli while not harming the survival rate, development, and biological functions of zebrafish embryos. We envision that our antibacterial strategy based on utilization of sacrificial Mg alloys could broaden the current palette of antibacterial platforms for metals.

Stem cell transplantation has been a promising treatment for peripheral arterial diseases in the past decade. Stem cells act as living bioreactors of paracrine factors that orchestrate tissue regeneration. Prestimulated adipose-derived stem cells (ADSCs) have been proposed as potential candidates but have been met with challenges in activating their secretory activities for clinical use. Here, we propose that tethering the ADSC surface with nanoparticles releasing tumor necrosis factor α (TNFα), named nanostimulator, would stimulate cellular secretory activity in situ. We examined this hypothesis by complexing octadecylamine-grafted hyaluronic acid onto a liposomal carrier of TNFα. Hyaluronic acid increased the liposomal stability and association to CD44 on ADSC surface. ADSCs tethered with these TNFα carriers exhibited up-regulated secretion of proangiogenic vascular endothelial growth factor and immunomodulatory prosteoglandin E2 (PGE(2)) while decreasing secretion of antiangiogenic pigment epithelium-derived factors. Accordingly, ADSCs tethered with nanostimulators promoted vascularization in a 3D microvascular chip and enhanced recovery of perfusion, walking, and muscle mass in a murine ischemic hindlimb compared to untreated ADSCs. We propose that this surface tethering strategy for in situ stimulation of stem cells would replace the costly and cumbersome preconditioning process and expedite clinical use of stem cells for improved treatments of various injuries and diseases.

We aimed to design and manufacture a transporter capable of delivering small interfering RNAs (siRNAs) into the skin without causing any damage. &beta, glucans are unique chiral polysaccharides with well-defined immunological properties and supramolecular wrapping ability. However, the chiral properties of these polymers have hardly been applied in drug delivery systems. In this study, &beta, glucan nanoparticles were designed and manufactured to deliver genetic material to the target cells. The &beta, glucan molecules were self-assembled with an siRNA into nanoparticles of 300&ndash, 400 nm in diameter via a conformational transition process, in order to construct a gene delivery system. The assembled gene nanocarriers were associated with high gene-loading ability. The expression and efficiency of siRNA were verified after its delivery via &beta, glucan. Our results provide evidence that &beta, glucan nanoparticles can be effectively used to deliver siRNA into the cells.

Biological responses on biomaterials occur either on their surface or at the interface. Therefore, surface characterization is an essential step in the fabrication of ideal biomaterials for achieving effective control of the interaction between the material surface and the biological environment. Herein, we applied femtosecond laser ablation on electrospun fibrous scaffolds to fabricate various hierarchical patterns with a focus on the alignment of cells. We investigated the simultaneously stimulated response of cardiomyoblasts based on multiple topographical cues, including scales, oriented directions, and spatial arrangements, in the fibrous scaffolds. Our results demonstrated a synergistic effect on cell behaviors of one or more structural arrangements in a homogeneous orientation, whereas antagonistic effects were observed for cells arranged on a surface with heterogeneous directions. Taken together, these results indicate that our hierarchically patterned fibrous scaffolds may be useful tools for understanding the cellular behavior on fibrous scaffolds used to mimic an extracellular matrix-like environment. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1732-1742, 2018.

A monolayer of endothelial cells (ECs) aligned along the direction of blood flow plays crucial roles in the regulation of anti-thrombogenic and pro-inflammatory reactions in the blood vessel wall. Thus, many researchers have attempted to mimic the aligned structure of ECs in vascular grafts or tissue-engineered blood vessels. In the present study, we fabricated micro-groove patterned nanofibers using a femtosecond laser ablation technique to recapitulate the densely organized anisotropic architecture of the endothelial layer. Femtosecond laser ablation enabled us to generate high-resolution groove patterns (10 μm width) with 20 or 80 μm gaps on randomly oriented electrospun nanofibers. The patterned nanofibers exhibited anisotropic (transverse: 101.1 ± 4.0° and longitudinal: 123.5 ± 9.4°) water contact angles; however, the mechanical properties were consistent in both directions. The micropatterned nanofibers modulated the aligned structure or aspect ratio (20 μm: 0.23 ± 0.11 and 80 μm: 0.42 ± 0.18) of ECs along the pattern direction. In particular, the engineered aligned endothelial layer was effective in eliciting an anti-inflammatory response (approximately 50% greater than that of random or aligned nanofibers), thereby effectively preventing monocyte adhesion following activation by TNF-α treatment. Therefore, micropatterning by laser ablation can be utilized to generate high-resolution microgrooves on various substrates, thereby providing fundamental platforms for vascular tissue engineering.

Controlling the interactions of light with matter is crucial for the success and scalability of materials-processing applications. When ultrashort pulsed lasers are used, the optimal interplay between the laser and the material parameters enable highly precise and controllable fabrication, allowing structuring down to the nanometer scale. Besides this, a unique aspect for many applications is the possibility of material modifications at multiple length scales, leading to complex micro- and nanoscale architectures, while adding a new dimension to optimization of the structures. As a result, femtosecond laser micro-/nanoprocessing offers unique capabilities for three-dimensional, material-independent modification, opening new opportunities for innovation and exploitation in the materials industry. This article focuses on the implementation of ultrashort pulsed laser-based micro- and nanofabrication methodologies for the realization of structures relevant to biomimetic, fluidic, and biological applications. The wealth of possibilities and the number of new approaches for obtaining complex high-resolution features at the micro- and nanoscales are demonstrated.

A new antibacterial strategy for Ti has been developed without the use of any external antibacterial agents and surface treatments. By combining Mg alloys with Ti, H2O2, which is an oxidizing agent that kills bacteria, was spontaneously generated near the surface of Ti. Importantly, the H2O2 formation kinetics can be precisely controlled by tailoring the degradation rates of Mg alloys connected to Ti. Through microstructural and electrochemical modification of Mg with alloying elements (Ca, Zn), the degradation rates of Mg alloys were controlled, and the H2O2 release kinetics was accelerated when the degradation rate of Mg alloys increased. With the introduction of an in vivo assessment platform comprised of Escherichia coli (E. coli) and transgenic zebrafish embryos, we are able to design optimized antibacterial systems (Ti-Mg and Ti-Mg-3wt% Zn) that can selectively eradicate E. coli while not harming the survival rate, development, and biological functions of zebrafish embryos. We envision that our antibacterial strategy based on utilization of sacrificial Mg alloys could broaden the current palette of antibacterial platforms for metals.